Differential Control of Calcium Homeostasis and Vascular Reactivity by Ca2+/Calmodulin-Dependent Kinase II

Anand M PRASAD; Daniel W NUNO; Curt D SIGMUND; Mark E ANDERSON; Kathryn G LAMPING; Isabella M GRUMBACH; Olha M KOVAL; Pimonrat KETSAWATSOMKRON; WEIWEI LI; HUI LI; Fred Y SHEN; Mei-Ling A JOINER; William KUTSCHKE; Robert M WEISS

doi:10.1161/HYPERTENSIONAHA.113.01508

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Differential Control of Calcium Homeostasis and Vascular Reactivity by Ca2+/Calmodulin-Dependent Kinase II

Journal article

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Differential Control of Calcium Homeostasis and Vascular Reactivity by Ca2+/Calmodulin-Dependent Kinase II

Anand M PRASAD, Daniel W NUNO, Curt D SIGMUND, Mark E ANDERSON, Kathryn G LAMPING, Isabella M GRUMBACH, Olha M KOVAL, Pimonrat KETSAWATSOMKRON, WEIWEI LI, HUI LI, …

Hypertension (Dallas, Tex. 1979), Vol.62(2), pp.434-441

2013

DOI: 10.1161/HYPERTENSIONAHA.113.01508

PMID: 23753415

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Abstract

The multifunctional Ca(2+)/calmodulin-dependent kinase II (CaMKII) is activated by vasoconstrictors in vascular smooth muscle cells (VSMC), but its impact on vasoconstriction remains unknown. We hypothesized that CaMKII inhibition in VSMC decreases vasoconstriction. Using novel transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), we investigated the effect of CaMKII inhibition on L-type Ca(2+) channel current (ICa), cytoplasmic and sarcoplasmic reticulum Ca(2+), and vasoconstriction in mesenteric arteries. In mesenteric VSMC, CaMKII inhibition significantly reduced action potential duration and the residual ICa 50 ms after peak amplitude, indicative of loss of L-type Ca(2+) channel-dependent ICa facilitation. Treatment with angiotensin II or phenylephrine increased the intracellular Ca(2+) concentration in wild-type but not TG SM-CaMKIIN VSMC. The difference in intracellular Ca(2+) concentration was abolished by pretreatment with nifedipine, an L-type Ca(2+) channel antagonist. In TG SM-CaMKIIN VSMC, the total sarcoplasmic reticulum Ca(2+) content was reduced as a result of diminished sarcoplasmic reticulum Ca(2+) ATPase activity via impaired derepression of the sarcoplasmic reticulum Ca(2+) ATPase inhibitor phospholamban. Despite the differences in intracellular Ca(2+) concentration, CaMKII inhibition did not alter myogenic tone or vasoconstriction of mesenteric arteries in response to KCl, angiotensin II, and phenylephrine. However, it increased myosin light chain kinase activity. These data suggest that CaMKII activity maintains intracellular calcium homeostasis but is not required for vasoconstriction of mesenteric arteries.

Cardiology. Vascular system

Biological and medical sciences

Arterial hypertension. Arterial hypotension

Medical sciences

Blood and lymphatic vessels

Details

Title: Subtitle: Differential Control of Calcium Homeostasis and Vascular Reactivity by Ca2+/Calmodulin-Dependent Kinase II
Creators: Anand M PRASAD - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Daniel W NUNO - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Curt D SIGMUND - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Mark E ANDERSON - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Kathryn G LAMPING - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Isabella M GRUMBACH - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Olha M KOVAL - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Pimonrat KETSAWATSOMKRON - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
WEIWEI LI - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
HUI LI - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Fred Y SHEN - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Mei-Ling A JOINER - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
William KUTSCHKE - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Robert M WEISS - Department of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.62(2), pp.434-441
Publisher: Lippincott Williams & Wilkins
DOI: 10.1161/HYPERTENSIONAHA.113.01508
PMID: 23753415
ISSN: 0194-911X
eISSN: 1524-4563
Language: English
Date published: 2013
Academic Unit: Molecular Physiology and Biophysics; Pathology; Cardiovascular Medicine; Biology; Radiation Oncology; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984094212202771

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